Our research program is aimed at the development of a model eucaryotic system combining genetic and biochemical approaches for the analysis of three interrelated cellular phenomena; DNA replication, DNA repair and recombination. Our genetic approach focuses on the isolation and characterization of mutagen-sensitive strains of Drosophila melanogaster on the notion that strains with such heritable defects will have aberrations in the cellular systems under study. Experiments to date have concentrated on the isolation of X-linked, methyl methanesulfonate-sensitive strains and thirteen confirmed sensitives have been isolated. Preliminary characterizations have indicated that the strains exhibit sensitivities to additional mutagens, particularly X-rays and ultraviolet light, enhanced induced mutagenesis rates and defects in recombination and chromosome segregation. Biochemical studies have been concerned with the investigation of wild type parameters associated with the systems being investigated, as a foundation for comparison with mutagen-sensitive strains. Two approaches have been employed: (1) a study of the number and kinds of DNA polymerizing activities in various stages of the life cycle; and, (2) an analysis of the number and kinds of proteins which exhibit an affinity for DNA. Investigations to date have uncovered one major DNA polymerase activity and, possibly one minor activity, from both larval and pupal extracts examined by DNA cellulose chromatography. DNA cellulose chromatography coupled with SDS-acrylamide electrophoresis procedures have revealed 20-25 polypeptide bands which exhibit an affinity for DNA binding. Continuation of these studies should provide significant insights into the nature of the cellular events under investigation.